Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are common and often disabling conditions affecting many veterans of Operations Iraqi Freedom (OIF), Enduring Freedom (OEF), and New Dawn (OND). Emerging evidence suggests that both conditions are associated with elevated levels of central and peripheral oxidative stress (OXS) and inflammation (INF). For this proposal, we have assembled a unique team of investigators with expertise in molecular genetics and magnetic resonance spectroscopy (MRS) to study these processes in relation to chronic PTSD and mTBI. The study will draw from a large and psychiatrically heterogeneous cohort of veterans of OIF/OEF/OND, now on average 10 years post-deployment, with genome-wide genotype data available from a previous assessment. We will acquire new MRS scans for analysis in combination with the genomic data to examine associations of PTSD and mTBI with neural and peripheral indices of OXS and INF and identify genomic sources of individual differences in these associations. More specifically, the primary aims are to (a) examine associations between current PTSD, history of mTBI, and MRS measures of OXS and INF, (b) interrogate genes in the OXS and INF pathways to identify genetic moderators of the associations between PTSD, mTBI and MRS parameters, and (c) examine associations between MRS measures of OXS and INF, other MRI indices of neural integrity, and peripheral markers of OXS and INF. The ultimate goal of this study is to identify neurobiological pathways that can be used in the future to guide the development of blood panels and/or neuroimaging protocols for clinical assessment, as well as molecular targets for pharmacologic intervention for veterans suffering from chronic PTSD and mTBI.